A salt bridge in intracellular loop 2 is essential for folding of human p-glycoprotein.

A salt bridge in intracellular loop 2 is essential for folding of human p-glycoprotein.
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DOI:
10.1021/bi400425k
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发表时间:
2013-05-14
期刊:
影响因子:
2.9
通讯作者:
Clarke, David M.
Clarke, David M.
中科院分区:
生物学3区
文献类型:
--
作者:
Loo, Tip W.;Clarke, David M.

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目前尚无人P-糖蛋白(P-gp,ABCB1)药物泵的高分辨结构。基于小鼠和秀丽线虫P-GPS晶体结构的同源模型表明,细胞内环2(ICL2,在第一个跨膜区)和第二个核苷酸结合区之间存在广泛的接触。以这些P-gp结构为模型的人P-gp产生不同的ICL2结构。只有基于线虫P-gp结构的模型才能预测盐桥的存在。我们发现Glu256-Arg276盐桥是P-gp折叠的关键。
There is no high-resolution structure of the human P-glycoprotein (P-gp, ABCB1) drug pump. Homology models based on the crystal structures of mouse and Caenorhabditis elegans P-gps show extensive contacts between intracellular loop 2 (ICL2, in the first transmembrane domain) and the second nucleotide-binding domain. Human P-gp modeled on these P-gp structures yields different ICL2 structures. Only the model based on the C. elegans P-gp structure predicts the presence of a salt bridge. We show that the Glu256–Arg276 salt bridge was critical for P-gp folding.
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